chr17-73260957-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001129885.1(CPSF4L):āc.130T>Gā(p.Phe44Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,550,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 33)
Exomes š: 0.000033 ( 0 hom. )
Consequence
CPSF4L
NM_001129885.1 missense
NM_001129885.1 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 5.34
Genes affected
CPSF4L (HGNC:33632): (cleavage and polyadenylation specific factor 4 like) Predicted to enable RNA binding activity and metal ion binding activity. Predicted to be involved in pre-mRNA cleavage required for polyadenylation. Predicted to be part of mRNA cleavage and polyadenylation specificity factor complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.9
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPSF4L | NM_001129885.1 | c.130T>G | p.Phe44Val | missense_variant | 2/6 | ENST00000344935.8 | |
CPSF4L | XM_011525115.3 | c.196T>G | p.Phe66Val | missense_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPSF4L | ENST00000344935.8 | c.130T>G | p.Phe44Val | missense_variant | 2/6 | 1 | NM_001129885.1 | P1 | |
CPSF4L | ENST00000397671.1 | c.-63T>G | 5_prime_UTR_variant | 2/7 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000649 AC: 1AN: 154178Hom.: 0 AF XY: 0.0000122 AC XY: 1AN XY: 81800
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GnomAD4 exome AF: 0.0000329 AC: 46AN: 1398360Hom.: 0 Cov.: 29 AF XY: 0.0000261 AC XY: 18AN XY: 689690
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152152Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74330
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2022 | The c.130T>G (p.F44V) alteration is located in exon 2 (coding exon 2) of the CPSF4L gene. This alteration results from a T to G substitution at nucleotide position 130, causing the phenylalanine (F) at amino acid position 44 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of stability (P = 0.0491);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at